Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice.

Area of Science:

• Neuroscience
• Vascular Biology
• Stroke Research

Background:

• Blood-brain barrier (BBB) dysfunction is central to neurological diseases.
• Platelet-derived growth factor receptor-alpha (PDGFRα) plays a role in hemorrhagic transformation after stroke.
• PDGF signaling is a potential therapeutic target for BBB dysfunction.

Purpose of the Study:

• To investigate the role of PDGF signaling in tissue remodeling following middle cerebral arterial occlusion (MCAO) in mice.
• To determine the specific contribution of PDGFRα to BBB integrity and stroke outcomes.

Main Methods:

• Administration of imatinib (PDGFR inhibitor) in wild-type mice after permanent MCAO.
• Generation and use of PDGFRα conditional knockout (C-KO) mice in transient MCAO models.
• Assessment of lesion size, hemorrhagic transformation, IgG leakage, tight junction proteins, pericyte coverage, and TGF-β1/MMP9 expression.

Main Results:

• Imatinib treatment increased lesion size and hemorrhagic transformation in the subacute phase post-MCAO.
• C-KO mice exhibited augmented hemorrhagic transformation and IgG leakage in the subacute phase.
• PDGFRα signaling, potentially mediated by TGF-β1, demonstrated protective effects against BBB dysfunction in the subacute stroke phase.

Conclusions:

• PDGFRα signaling is crucial for protecting the BBB during the subacute phase of ischemic stroke.
• Targeting PDGFRα may offer therapeutic benefits for mitigating stroke-induced BBB damage.
• TGF-β1 may mediate the protective effects of PDGFRα signaling on the BBB.